Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against “self”. In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients’ life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.

Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs / M. Perrino, E. Voulaz, S. Balin, G. Cazzato, E. Fontana, S. Franzese, M. Defendi, F. De Vincenzo, N. Cordua, R. Tamma, F. Borea, M. Aliprandi, M. Airoldi, L. Cecchi, R. Fazio, M. Alloisio, G. Marulli, A. Santoro, L. Di Tommaso, G. Ingravallo, L. Russo, G. Da Rin, A. Villa, S. Della Bella, P. Zucali, D. Mavilio. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 15:(2024), pp. 1288045.1-1288045.14. [10.3389/fimmu.2024.1288045]

Autoimmunity in thymic epithelial tumors: a not yet clarified pathologic paradigm associated with several unmet clinical needs

S. Balin;S. Franzese;S. Della Bella
Penultimo
;
D. Mavilio
Co-ultimo
2024

Abstract

Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against “self”. In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients’ life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.
thymic epithelial tumors; autoimmunity; myasthenia gravis; immunotherapy; surgery; thymopoiesis
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
Settore MED/04 - Patologia Generale
Settore MED/50 - Scienze Tecniche Mediche Applicate
Settore MED/06 - Oncologia Medica
Settore MED/21 - Chirurgia Toracica
   Targeting the overlapping mechanisms inducing immune cell dysfunctions and autoimmunity in the pathophysiology of Thymic Epithelial Tumors.
   MINISTERO DELL'UNIVERSITA' E DELLA RICERCA
   2022R7PMJP_001
2024
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1043431
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